Hyperpolarised glutamine as a biomolecular metabolism tracker – PolarGlu

This project aims at developing methods and hardware in nuclear magnetic resonance (NMR) spectroscopy enhanced by dissolution dynamic nuclear polarisation (D-DNP) to study in real time the cellular metabolism of glutamine.

This amino acid and its metabolism is involved in cellular energetic pathways and also play a role in the development of some cardiac pathologies, which makes it a potential biological tracker of choice for medical imaging through MRI or for fluxomics experiments. However, as NMR suffers from an intrinsic low sensitivity, following enzymatic reactions and cell metabolism in real-time can prove to be a challenge. This is why this project aims at implementing D-DNP experiments dedicated to the study of glutamine to benefit from signal enhancements of several orders of magnitude enabled by this hyperpolarisation technique.

The project will include four main work packages to address specific challenges of the real time D-DNP experiments that are considered:
- Hardware development for the dissolution and injection in order to address specifically living cells;
- Optimization of the formulation of the D-DNP sample of glutamine in order to obtain more concentrated samples which at the same time achieve high levels of polarisation;
- Development of new dedicated pulse sequences (for instance selective excitation or TOCSY mixing blocks) to exploit the gains of sensitivity brought by D-DNP and the two first work packages;
- Experiments in vitro and on live cellular cultures to study the metabolism of glutamine and benefiting from the developments of the three previous work packages. Experiments shall be performed on healthy and diseased cell models, as well as in absence or in presence of anti-metabolic drugs. Proof of concept MRI experiments are foreseen to probe the cardiac metabolism of glutamine.